tbuckley/cabot-search huggingface dataset:
Addressing suicidal ideation in oncology patients.
Authors: Lyndsey Sandow, Ryan Friedman, Neha Agrawal, Julie N. Graff, Rajat Thawani
Journal: Journal of Clinical Oncology (2023)

e13534 Background: The diagnosis of cancer leads to worsening a patient’s physical, mental, personal stressors and inevitably can lead to patients questioning their mortality. Cancer is the leading cause of death in the United States, and the diagnosis and treatment of cancer can be very difficult for patients from a physical, psychosocial, and financial perspective. Suicide is the 10th leading cause of death in the United States and risk factors for suicide include family history of suicide, previous suicide attempts, feelings of hopelessness, and depression. In addition to these important risk factors, a recent study including 8.6 million cancer patients showed that risk of suicide is four times greater in cancer patients than the general population. Despite this elevated risk, the detection of cancer patients at highest risk of suicide is poor and there are limited resources to help providers risk stratify cancer patients at highest risk of suicide. Methods: We conducted a cross sectional study of Portland VA oncology providers (physicians, housestaff, advanced practice providers, nurses and social workers) to determine the frequency in which those providers work with oncology patients struggling with suicidal ideation, the frequency of screening completed by the oncology providers, and the barriers to screening patients for suicidal ideation during a regular office visit. Qualtrics surveys were sent to all VA oncology providers. A significance test for proportions was utilized to determine the statistical validity of the results. Results: A total of 22 providers completed the survey. The majority of respondents were MD/DOs (n=13 We showed that most providers have cared for patients affected by suicidal ideation including attempted suicide and completed suicide attempts (p &lt; 0.05). While most providers answered that they had screened patients for suicide before all respondents noted significant barriers to screening patients. The majority of respondents identified multiple barriers to addressing suicidality with almost all respondents included “not enough time” as one of the barriers. Other prominent barriers included, “unsure of next steps”, “not having proper tools to assess”, “not having expertise to assess”. Conclusions: Our study showed that most oncology providers will care for patients affected by suicidal ideation during their career. In addition it shows that while many providers have screened patients for suicidal ideation, most providers face significant barriers to doing so during a clinic visit. Our study contributes to the current body of knowledge by identifying the significant barriers faced in the providers in the Portland VA oncology clinic.
The impact of response-directed surgery and adjuvant therapy on long-term survival after neoadjuvant ipilimumab plus nivolumab in stage III melanoma: Three-year data of PRADO and OpACIN-neo.
Authors: Irene L.M. Reijers, Alexander M. Menzies, Judith M. Versluis, Robyn P.M. Saw, Winan J. van Houdt, Ellen Kapiteijn, Astrid Aplonia Maria Van Der Veldt, Karijn Suijkerbuijk, Hanna Eriksson, Geke Hospers, Willem M.C. Klop, Marta I. Lopez-Yurda, Lindsay G. Grijpink-Ongering, Maria Gonzalez, Andrew John Spillane, Richard A. Scolyer, Bart A. van de Wiel, Alexander Christopher Jonathan Van Akkooi, Georgina V. Long, Christian U. Blank
Journal: Journal of Clinical Oncology (2023)

101 Background: Neoadjuvant ipilimumab (IPI) + nivolumab (NIVO) has been shown to induce high pathologic response rates associated with an excellent relapse-free survival (RFS) in high-risk stage III melanoma. While OpACIN-neo tested different neoadjuvant IPI + NIVO regimens followed by therapeutic lymph node dissection (TLND) without adjuvant systemic therapy (ST), PRADO tested a personalized approach. In patients (pts) achieving a major pathologic response (MPR; ≤10% viable tumor), TLND and adjuvant ST were omitted, and pts with pathologic non-response (pNR; &gt;50% viable tumor) were treated with adjuvant ST (BRAFi/MEKi or anti-PD1) ± radiotherapy after TLND. Here, we address 1) whether omitting TLND in MPR pts had an adverse effect on long-term survival and 2) whether adding adjuvant ST in pNR pts had a favorable effect on survival. Methods: The 3-year (3y) RFS and distant metastasis-free survival (DMFS) of pts with MPR and pNR from PRADO and OpACIN-neo were analyzed, comparing MPR pts with TLND versus without TLND and pNR pts with adjuvant ST versus without adjuvant ST. Survival rates were calculated and compared with Kaplan-Meier and log-rank methods. Associations between baseline characteristics and RFS or DMFS were examined by Cox regression analysis. Results: Median follow-up was 37.9 months in PRADO (cutoff Jan 8, 2023) and 46.8 months in OpACIN-neo (cutoff Feb 14, 2022). For MPR pts, TLND omission did not affect survival, with a 3y RFS of 93% versus 96% (p=0.47) and 3y DMFS 98% versus 98% (p=0.92) for pts without TLND (n=59) versus with TLND (n=53), respectively. In pNR pts, an indication for a RFS and DMFS benefit was seen favoring pts with adjuvant ST (n=17: n=10 BRAFi/MEKi and n=7 anti-PD1) over pts without adjuvant ST (n=23), with 3y RFS rates being 64% versus 35% (p=0.10) and 3y DMFS rates 70% versus 52% (p=0.24). Baseline clinical characteristics did not differ between PRADO and OpACIN-neo pts or were not associated with RFS and DMFS. Conclusions: Omitting TLND in MPR pts after neoadjuvant IPI + NIVO seems not to affect RFS/DMFS. Given the high survival rates, adjuvant ST is unlikely to give further benefit in these pts. In pts with pNR, addition of adjuvant ST with ongoing anti-PD1 or switch to BRAFi/MEKi appears to improve RFS and DMFS. Clinical trial information: NCT02977052 . [Table: see text]
Olaparib (O) in advanced triple negative breast cancer (aTNBC) patients (pts) with BRCA1/2 promoter methylation: GEICAM/2015-06 study (COMETA-Breast).
Authors: Juan De La Haba, Antonio Anton, Vanesa Quiroga, Angel Guerrero, Raquel Andrés, Mireia Mele, Santiago Gonzalez- Santiago, Jose Alejandro Perez-Fidalgo, Teresa Ramon y Cajal, Maria Jose Escudero, Susana Bezares, Rosalia Caballero, Federico Rojo
Journal: Journal of Clinical Oncology (2023)

1093 Background: Epigenetic silencing by aberrant BRCA1/2 promoters’ methylation ( BRCA-meth) can be responsible for a dysfunctional BRCA protein. BRCA-meth occurs in 15-57% of TNBC pts. BRCA-meth breast cancer (BC) display pathologic features and genetic profiles like germline BRCA1/2-mutated (g BRCA1/2m) carriers. O is a PARP inhibitor approved for treating g BRCAm HER2-negative advanced BC (aBC) pts. These are the results of a phase II study assessing the O efficacy in aTNBC pts with BRCA1/2-meth (NCT03205761). Methods: We included aTNBC pretreated pts (≥1 line) with centrally confirmed somatic BRCA1/2-meth (in most recent lesion(s) available) and no g BRCA1/2m. O 300mg b.i.d. was administered. BRCA1/2 CpG island was considered methylated if value was ≥25%. Overall response rate (ORR) (complete response [CR] + partial response [PR]) according to RECIST 1.1) was the primary objective. Thirty-one evaluable pts were required based on an optimal 2-stage Simon’s design (α error=0.05, 1-β error=80%), estimating an ORR increase of 24%, with a null hypothesis of 30%. Whole exome/transcriptome and 105-genes NGS assays (Tempus xE &amp; xF) were performed on pretreatment tumor and sequential ctDNA of a long-term responder. Results: Eleven pts received ≥1 cycle of O (ITT population). Median age was 51 years (37-64), and 8 pts were postmenopausal. All M0 pts at diagnosis had neo-/adjuvant chemotherapy (CT). Median O exposure duration was 8 (1-88) weeks and relative dose-intensity was 97% (76-100), with any dose modifications in 6 pts. ORR was 9% (1 PR/11; 95% CI, 0.2-41). Clinical benefit rate (CR + PR + stable disease of any duration) was 36% (4/11; 95% CI, 11-69). Most pts (n=9) discontinued O due to BC progression. Median PFS was 2 months (95% CI, 1-4), and median OS was 9 months (95% CI, 1-14). One pt with confirmed PR was on O for &gt;20 months. AEs were reported in 3 pts in line with O safety profile. No AE led to O discontinuation and no SAEs were reported. The statistical assumptions for the 1 st Simon’s model stage were not met (≥ 4/12 pts with CR or PR), so the recruitment did not proceed onto the 2 nd stage. Preliminary NGS analysis on the long-term responder identified alterations on tumor (TP53, BCL11A, MYC) and on-treatment ctDNA (PMS2). Conclusions: In this proof-of-concept study, O did not show clinically nor statistically significant antitumor activity in pretreated aTNBC pts with BRCA1/2-meth . Clinical trial information: NCT03205761 . [Table: see text]
Accelerated partial breast irradiation (APBI) for ductal carcinoma <i>in situ</i>.
Authors: Diana A Roth O'Brien, Lillian A Boe, Boris Mueller, John J Cuaron, Amy Xu, Michael B. Bernstein, Beryl McCormick, Simon N. Powell, Atif J. Khan, Lior Zvi Braunstein
Journal: Journal of Clinical Oncology (2023)

e12516 Background: Landmark studies of accelerated partial breast irradiation (APBI) included patients with DCIS, but with limited guidance regarding subgroups of in situ disease. Suitability criteria defined by national guidelines for APBI are narrowly constrained among those with DCIS, and controversy persists regarding optimal patient selection. Here, we report disease outcomes for a heterogeneous cohort of patients with DCIS who received APBI. Methods: Using a prospectively maintained institutional database, we identified patients with DCIS who underwent lumpectomy and adjuvant APBI from 2000 to 2022. Clinicopathologic characteristics were collected, and patients were classified as suitable, cautionary, or unsuitable for APBI by the latest American Society for Radiation Oncology (ASTRO) criteria. Outcomes of interest included local recurrence (LR), overall survival (OS), and follow up time. Cumulative incidence functions were calculated to estimate the incidence of LR over time. All statistical analyses were performed in R version 4.2.2. Results: The cohort comprised 176 patients, median age 60 years (IQR 52, 66). Median DCIS size was 9 mm (IQR 4, 15 mm), and approximately 20% had multifocal disease. Most patients had negative final surgical margins (160, 91%), with 10 patients having ≤2 mm margins and 6 having ≤1 mm margins for DCIS. 18 (10%) patients had nuclear grade I disease, 111 (63%) had grade II disease, and 33 (19%) had grade III disease, with a small subset classified as grade I-II or II-III. Most patients (161, 91%) had ER+ DCIS, and 72 (41%) received endocrine therapy. By ASTRO criteria, 118 (67%) patients were suitable for APBI, 57 (32%) cautionary, and 1 (0.6%) was unsuitable. At a median 24 months of follow up (range 2 to 127 months) we observed only one LR, yielding a 2-year LR rate of 0.6%. The LR occurred in the cautionary group, yielding a 2-year LR rate of 1.8% for the cautionary subset. The patient with LR was 56 years old, with 24 mm of high grade DCIS, ER+, with lumpectomy to negative margins, and did not receive endocrine therapy. No breast cancer mortality events were observed. Conclusions: Our early-term results exhibit excellent local control for patients with DCIS who received lumpectomy and APBI, even among those classified as “cautionary” by national guidelines. Although our findings are limited by short follow up, these results suggest that broadening the application of APBI for patients with DCIS may warrant further investigation.
Knowledge gaps and educational needs for common cancer therapy-related cardiovascular toxicities and related drug interactions.
Authors: Sarah Kaspari, Heather Moore, Craig Beavers, Sarah Maryon Hayes, Kristen Peterson, Israa Yaseen, Preston Skersick, Kelsey Truitt, Stephen Casselli, Jo Ellen E. Rodgers
Journal: Journal of Clinical Oncology (2023)

e13672 Background: Unprecedented growth in novel oncolytic agents has led to an increase in the complexity of cancer management, including cancer therapy-related cardiovascular toxicities (CTR-CVTs) and related pharmacodynamic (PD) and pharmacokinetic (PK) drug-drug interactions (DDIs). The intent of this survey is to assess the landscape of CTR-CVTs including health care provider (HCP) educational needs. Methods: A 20-question survey was distributed to HCPs primarily specializing in cardiology, oncology, hematology and cardio-oncology. The survey was distributed on email listservs of targeted organizations, including the International Cardio-Oncology Society. In addition to demographics, the survey assessed CTR-CVTs and related DDIs encountered. Perceived knowledge gaps were also assessed. Data was analyzed and summarized utilizing descriptive statistics. Results: Of 220 survey respondents, 46% were pharmacists and 54% were other HCPs ( &gt; 80% physicians). Respondents predominately practiced in North America (59%) or Europe (20%), with the majority at academic medical centers (65% academic, 35% community) and primarily specializing in cardiology (71%, cardiology, 26% oncology, 14% hematology). Types of malignancies managed were primarily solid tumors (74%), however hematological malignancy management was also common ( &gt; 60%). All HCPs reported encountering the following CTR-CVTs most commonly: cancer therapy-related cardiac dysfunction (CTRCD) (88%), hypertension (HTN) (79%) and thromboembolic disease (71%). Overall, pharmacists reported managing CTR-CVTs less frequently than other HCPs, especially regarding atrial fibrillation/flutter, coronary artery disease/vasospasm and bradycardia/AV block. The most common cardio-oncology-related PD DDIs encountered were CTRCD and QT prolongation/Torsades de Pointes (QTP/TdP). The most frequently managed cardio-oncology-related PK DDIs included antiarrhythmic agents, direct-acting oral anticoagulants and antiplatelet agents. All HCPs reported greatest comfort managing anthracycline/HER2 targeted therapy-associated CTRCD and least comfort managing arsenic-associated QTP. Immune checkpoint inhibitor-associated myocarditis (74%), immune modulator-associated thrombosis/thrombotic events (64%), Bruton tyrosine kinase inhibitor associated bleeding (58%) and atrial fibrillation (55%) were ranked of highest educational need. Overall, responses for PD/PK DDIs and educational recommendations were similar between pharmacists and other HCPs. Conclusions: This survey provides insight on the most commonly encountered CTR-CVTs and related DDIs as well as knowledge gaps of HCPs managing CTR-CVTs. These specific areas should be targeted for future educational initiatives to optimize the cardiovascular care of patients with cancer.
Comparative assessment of manual chart review and patient-level adverse drug event identification using artificial intelligence in evaluating immunotherapy-related adverse events (irAEs).
Authors: Md Muntasir Zitu, Lang Li, Mohamed I. Elsaid, Margaret Elena Gatti-Mays, Ashish Manne, Aditi Shendre
Journal: Journal of Clinical Oncology (2023)

e13583 Background: IrAEs monitoring in patients undergoing Immune checkpoint inhibitor (ICI) treatments relies on analyzing clinical notes and structure data from electronic health records. As IrAEs are not yet fully captured in the ICD claims, they could be under reported. On the other hand, IrAEs are usually recorded in the clinical notes. A natural language processing (NLP) tool is highly desirable to extract them from clinical notes. In this study, we aim to compare the performance of our machine learning (ML) NLP model in IrAE extraction against 1) manual chart reviews and 2) ICD claims data. Methods: The study validation set included 194 newly diagnosed stage I-VI gastrointestinal cancer patients treated with ICIs at the Ohio State University Comprehensive Cancer Center. An irAE was defined as the occurrence of gastrointestinal, pulmonary, dermatological, or endocrine adverse events post-ICI infusion. Our NLP ML model was trained on 1230 clinical notes from 20 positive (who had ADEs) and 10 negative (who did not have ADEs) patients who received ICIs. ICD irAE method is based on ICD-9 and ICD-10 codes, which identifies irAEs post-ICI infusions. All manual reviews of ICI induced irAEs were done by a medical oncologist specializing in gastrointestinal cancers and included patient charts, labs, and imaging post-ICI infusions. Results: In this 194 patient cohort, the median age was 61 years, 68% males, 89% White non-Hispanics, and 29% had colorectal cancer. The study included 8,500 medical notes with a median 29 notes per patient and 1,283 words per note. An estimated 4,726 (55.6%) were progress notes, 1,178 (13.9%) patient Instructions, and 430 (5.1%) consults. The incidences of irAEs were 13.9%, 25.8%, and 27.3%, respectively, using manual reviews, the ML model, and ICD claims, respectively. Compared to the manual reviews, the ML model had a 78% sensitivity, 83% specificity, 0.17 false positive rate (FPR), and 0.80 (95% CI, 0.72 to 0.89) area under the curve (AUC). In contrast, ICD claims had a poor agreement compared to manual reviews. 52% sensitivity, 77% specificity, 0.23 FPR, and AUC 0.64 (95% CI, 0.54 to 0.74). Conclusions: Using clinical notes, ML can identify patients with irAEs with a great potential to infer causality in real time clinical practice. Our irAE manual review analysis further indicates that ML model performance can be further improved if including lab and imaging data.
A comparison study of solid tumor, malignant hematology, and general medicine inpatient services.
Authors: Antonio Giuseppe Faieta, Amir Mortazavi, Claire F. Verschraegen, Marium Husain
Journal: Journal of Clinical Oncology (2023)

e13532 Background: One of the most important cancer centers in Ohio experienced an explosive growth in the number of inpatient admissions, with numerous inpatient services created between 2010 and 2022. In this abstract, we present how some financial and quality measures performed during this rapid expansion. Methods: Slicer-Dicer aggregate data was used to compare financial performance and quality measures of oncologic and general medicine inpatient (IP) services over time. General medicine services do not include the cancer and the heart disease populations, but there might be a small overlap. The cancer population is served by 9 IP oncology services. The following SlicerDicer Filters were used. Population: IP admissions. Slices: populations include these study groups, 10 inpatient medical oncology (solid tumors) (MO), 6 inpatient malignant hematology (MH) (including 1 bone marrow transplant) services were compared to 10 general medicine (GM) services. Gynecologic and central nervous system tumors are served by other services and were excluded. Measures: number of admissions, median and total payments (actual payment received), median and total expected reimbursement (reimbursement expected for DRG), mortality, readmission rates, average length of stay (LOS), percentage of patients with Medicaid, percentage of patients with Medicare. Dates: from 2011 to 2022 data. For some measures, quarterly data is presented rather than yearly data for graph simplicity. Results: The number of inpatient admissions grew by 90.77%, 130.55%, and 105.58% for GM, MO, and MH, respectively. The total expected reimbursement increased by 6.22%, 13.56% and decreased by 17.14% for GM, MO and MH, respectively. The total payment received grew by 314.29%, 283.69%, 86.80%, for MO, MH, and GM, respectively. MO, GM, and HM had a median payment increase of 76.51%, 51.96%, 20.74%, respectively. Mortality dropped for MO by 32.11%, from 76.9% to 52.2%, for MH by 49.46%, from 55.6% to 28.1% and in GM by 73.80% from 35.5 % to 9.3%. The average length of stay was 1 to 2 days longer in the MH and GM (respectively) compared to MO, with an increase from 2011 to 2022 for GM and MO, but a decrease for MH. Readmission rates decreased from 17.4% to 15.1% for MO, 12.7% to 10.3% for MH, and 14.9 to 12.5% for GM. In 2014, the percentage of Medicaid population increased in GM, and decreased in the oncology services (MO and MH) reaching 35% and 14% of the admitted patient population in 2022, respectively. Percentage of Medicare patients increased from 36.9% to 52.9%, 39.6% to 44.9%, and remained stable for MO, HM, and GM, respectively. Hospice discharge fluctuated between 1.2-1.6%, 2.5-5%, 8-12.9% of the discharged patients in GM, MH, and MO, respectively. Conclusions: In this abstract, we present a decade-trend data of important measures of inpatient oncology units.
Post-pandemic outlook of the oncology clinical trial landscape.
Authors: Jyoti Pant, Aparna Jadhav, Roshan Seth, Gayathri Raghupathy
Journal: Journal of Clinical Oncology (2023)

e13549 Background: The oncology clinical trials have grown gradually until 2019. The COVID-19 pandemic led to a marked reduction in clinical trial numbers. To understand the post-pandemic oncology landscape, we analyzed recent clinical trials between 2021 and 2022. Methods: The analytics and insights were obtained from the Kognitic digital platform for 2021 and 2022 (extracted-January 2023). The Kognitic platform applies proprietary Natural Language Processing (NLP) to extract cancer clinical trials from NIH’s clinicaltrials.gov (https://clinicaltrials.gov/ct2/home) and World Health Organization international trials registry ( https://trialsearch.who.int/utn.aspx ). A list of cancer-related synonyms and keywords was used with the NLP algorithm to extract the trials and generate a normalized list which was used for quality check to classify and add to the Kognitic drug database. Results: 14,361 national and international clinical trials launched in 2021 and 2022 were collected and analyzed. Of 14,361 trials, 3906 did not have trial phase information and were excluded from further analysis. We observed a reduction in overall clinical trial numbers in 2022 compared to 2021, with 8000 trials in 2021 and 6361 trials in 2022. In 2021, there were 799 Early Phase trials, 1043 Phase I, 2665 Phase II, 971 Phase III, and 425 Phase IV trials. In 2022, there were 340 Early Phase, 1037 Phase I, 2375 Phase II, 617 Phase III, and 183 Phase IV trials. Of these five Phases, Phase II had the highest number of trials in both 2021 and 2022. Similar to the total number of trials, we observed a general trend of decreasing trial count in all Phases (except Phase I) in 2022 compared to 2021. These trials were distributed across 21 indications, with the highest trial count in gastrointestinal cancer for both years. Out of the total trials, 24.18% of trials in 2021 and 22.93% in 2022 were gastrointestinal cancer trials. Other leading indications were lung cancer, non-Hodgkin lymphoma, breast cancer, and gynecologic cancers. Although the top indications remain the same in 2021 and 2022, there is a general trend of a decreasing number of trials in these indications in 2022. Next, we looked at the targets these trials were focused on. Our results show that Programmed Cell Death Protein 1 (PD-1) was the top target with the highest number of clinical trials, suggesting a continued broadening of the checkpoint inhibitor market. Similar to the total number of trials and the indications, we observed a general trend of decreasing clinical trials in each target in 2022 compared to 2021. Conclusions: Our results show a general trend of decreasing clinical trials in 2022 compared to 2021, suggesting that oncology clinical trials have not resumed pre-pandemic period growth. We observed a reduction in the number of clinical trials collectively and within various categories, namely, trial Phase, indications, and targets.